Method of preparing cyclic carbonates, cyclic carbamates, cyclic ureas, cyclic thiocarbonates, cyclic thiocarbamates, and cyclic dithiocarbonates

ABSTRACT

A method of preparing a cyclic monomer, comprising: forming a first mixture comprising a precursor compound, bis(pentafluorophenyl)carbonate, and a catalyst; wherein the precursor compound has a structure comprising a) two or more carbons, and b) two functional groups selected from the group consisting of primary amine, secondary amine, thiol group, hydroxyl group, and combinations thereof; and agitating the first mixture at a temperature effective to form a second mixture comprising the cyclic monomer, the cyclic monomer selected from the group consisting of a cyclic carbonate, a cyclic carbamate, a cyclic urea, a cyclic thiocarbonate, a cyclic thiocarbamate, and a cyclic dithiocarbonate.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of, and claims the benefit of,pending nonprovisional U.S. application Ser. No. 12/434,766 entitled“METHOD OF PREPARING CYCLIC CARBONATES, CYCLIC CARBAMATES, CYCLIC UREAS,CYCLIC THIOCARBONATES, CYCLIC THIOCARBAMATES, AND CYCLICDITHIOCARBONATES” filed on May 4, 2009, herein incorporated by referencein its entirety.

BACKGROUND

The present disclosure is generally related to a method of preparingcyclic monomers for ring-opening polymerizations, in particular cycliccarbonates, cyclic carbamates, cyclic ureas, cyclic thiocarbonates,cyclic thiocarbamates, and cyclic dithiocarbonates.

Technological advances continue to present many complex environmentalissues. As a consequence, pollution prevention and waste managementconstitute two significant challenges of the 21^(st) century. “Green”chemistry is a concept that is being embraced around the world to insurecontinued economic and environmental prosperity. The interest in theU.S. began with the passage of the Pollution Prevention Act of 1990, thefirst law focused on the source rather than the remediation of thepollutants, which prompted the U.S. Environmental Protection Agency(EPA) to establish its green chemistry program in 1991. Since then,modern synthetic methodologies are encouraged to preserve performancewhile minimizing toxicity, use renewable feedstocks, and use catalyticand/or recyclable reagents to minimize waste. Green chemistry is thedesign and development of chemical products/processes that reduce oreliminate the use of substances harmful to our health or environment.What makes green chemistry such a powerful concept is that it starts atthe molecular level and ultimately generates environmentally benignmaterials or material processes.

Phosgene is produced on a 10,000 ton scale per year for the formation ofisocyanates (for making polycarbamates), polycarbonates (e.g., bisphenolA polycarbonate), and the formation of acid chlorides. Although phosgeneis widely used, it is expensive and toxic. Phosgene was used in WorldWar I as a chemical weapon and has been involved in tragic industrialaccidents. Phosgene can be detected at 0.4 ppm which is only four timesthe U.S. maximum exposure limit. Phosgene is water-sensitive (reactingto form corrosive hydrogen chloride gas) and is therefore hazardous tostore, ship, and handle. Diphosgene (trichloromethyl chloroformate) andtriphosgene (bis(trichloromethyl)carbonate) are alternatives to phosgenewith higher boiling points. While these compounds can be used to performsimilar reactions with fewer handling difficulties, they still possesstoxicities similar to phosgene. Moreover, handling of phosgene andtri-phosgene is labor intensive, and reactions must be performed at −78°C. with exhaustive work ups. Reaction of an active-hydrogen compoundsuch as an alcohol, amine, or thiol with one of these phosgene-basedreagents produces hydrochloric acid. The highly acidic hydrochloric acidcan decompose acid-sensitive moieties in the starting material. Stepsmust be taken to scavenge this corrosive gas. These concerns addsubstantial cost to compounds produced with this reagent.

Known alternatives to phosgene include activated carbonyl compounds suchas p-nitrophenyl chloroformate, trichloromethyl chloroformate, carbonyldiimidazole, bis(o- or p-nitrophenyl)carbonate, andbis(2,4-nitrophenyl)carbonate. However, these reagents often suffer fromunwanted side reactions, difficult work ups, or lower reactivity.

Thus, a need exists for phosgene substitutes that are environmentallyless toxic, less costly, and more compatible with the general goals of“green” chemistry.

BRIEF SUMMARY

The current method addresses the need for a “green” phosgene substitutein the preparation of cyclic carbonates, cyclic carbamates, cyclicureas, cyclic thiocarbonates, cyclic thiocarbamates, and cyclicdithiocarbonates.

In one embodiment, a method of preparing a cyclic monomer comprisesforming a first mixture comprising a precursor compound,bis(pentafluorophenyl)carbonate, and a catalyst; wherein the precursorcompound has a structure comprising a) two or more carbons, and b) twofunctional groups selected from the group consisting of primary amine,secondary amine, thiol group, hydroxyl group, and combinations thereof;and agitating the first mixture at a temperature effective to form asecond mixture comprising the cyclic monomer, the cyclic monomerselected from the group consisting of a cyclic carbonate, a cycliccarbamate, a cyclic urea, a cyclic thiocarbonate, a cyclicthiocarbamate, and a cyclic dithiocarbonate.

In another embodiment, a method of preparing a cyclic monomer,comprising: forming a first mixture comprising abis(pentafluorophenyl)carbonate, a catalyst, and a precursor compound ofthe general formula (I):

wherein each X group independently represents OH, NHR″, NH₂, or SH; n is0 to 6; each R′ independently represents a hydrogen, a halide, an alkylgroup comprising 1 to 20 carbons, an ester group comprising 1 to 20carbons, an amide group comprising 1 to 20 carbons, an aryl groupcomprising 1 to 20 carbons, or an alkoxy group comprising 1 to 20carbons; and each R″ independently represents an alkyl group comprising1 to 20 carbons or an aryl group comprising 1 to 20 carbons; andagitating the first mixture at a temperature effective to form a secondmixture comprising the cyclic monomer, the cyclic monomer selected fromthe group consisting of a cyclic carbonate, a cyclic carbamate, a cyclicurea, a cyclic thiocarbonate, a cyclic thiocarbamate, and a cyclicdithiocarbonate.

In another embodiment, a method of preparing a cyclic monomer comprisesforming a first mixture comprising bis(pentafluorophenyl)carbonate, acatalyst, and a precursor compound of the general formula (13):

wherein X independently represents OH, NHR″, NH₂, or SH; R′ represents ahydrogen, a halide, an alkyl group comprising 1 to 20 carbons, an estergroup comprising 1 to 20 carbons, an amide group comprising 1 to 20carbons, an aryl group comprising 1 to 20 carbons, or an alkoxy groupcomprising 1 to 20 carbons; X′ represents O, S, NH, or NR″; R″ in X andX′ independently represents an alkyl group comprising 1 to 20 carbons oran aryl group comprising 1 to 20 carbons; R′″ represents an alkyl groupcomprising 1 to 20 carbons, or an aryl group comprising 1 to 20 carbons;and z is 0 or 1; and agitating the first mixture at a temperatureeffective to form a second mixture comprising the cyclic monomer, thecyclic monomer selected from the group consisting of a cyclic carbonate,a cyclic carbamate, a cyclic urea, a cyclic thiocarbonate, a cyclicthiocarbamate, and a cyclic dithiocarbonate.

Also disclosed is a biodegradable polymer derived from a cyclic monomerby ring-opening polymerization, the cyclic monomer derived frombis(pentafluorophenyl)carbonate.

Additional features and advantages are realized through the techniquesof the present invention. Other embodiments and aspects of the inventionare described in detail herein and are considered a part of the claimedinvention. For a better understanding of the invention with theadvantages and the features, refer to the description.

DETAILED DESCRIPTION

Disclosed is a method of preparing cyclic carbonates, cyclic carbamates,cyclic ureas, cyclic thiocarbonates, cyclic thiocarbamates, and cyclicdithiocarbonates using bis(pentafluorophenyl)carbonate (PFC), having thefollowing structure:

PFC is less toxic than phosgene. PFC is a crystalline solid at roomtemperature which, being less sensitive to water than phosgene, can beeasily stored, shipped, and handled. PFC does not require elaboratereaction and workup conditions. Moreover, the pentafluorophenolbyproduct produced during the disclosed cyclization reactions is lessvolatile, less acidic, and less corrosive than hydrochloric acid. Theseadvantages reduce the cost and complexity of the reactions, andpotentially widen the scope of the starting materials to includecompounds containing acid-sensitive groups. In addition, thepentafluorophenol byproduct can be readily recycled back into PFC.

Bis(pentafluorophenyl)carbonate has been used previously in thebioorganic community as a coupling agent for oligonucleotides (seeEfimov et al. Nucleic Acids Res. 1993, 21, 5337), for producing peptidemimics such as diazatides by Janda at Scripps (see: Bioorg. Med. Chem.1998, 8, 117-120; JACS, 1996, 118, 2539-2544; and U.S. Pat. No.6,664,372), and in the synthesis of N-carboxyanhydrides of amino acids(see: Fujita et al. J. Polym. Sci. A. Polym. Chem. 2007, 45, 5365-5369;and US Patent Publication 2007/0015932). However,bis(pentafluorophenyl)carbonate has not been used for the preparation ofcyclic carbonates, cyclic carbamates, cyclic ureas, cyclicthiocarbonates, cyclic thiocarbamates, and cyclic dithiocarbonates.

The method comprises forming a first mixture containing a cyclic monomerprecursor (referred to hereinafter as precursor compound) capable offorming a cyclic carbonate, cyclic carbamate, cyclic urea, cyclicthiocarbonate, cyclic thiocarbamate, or cyclic dithiocarbonate whenreacted with PFC. The precursor compound has the general formula (I):

where each X independently represents OH, NHR″, NH₂, or SH; n is 0 to 6,and R′ independently represents a hydrogen, a halide, an alkyl groupcomprising 1 to 20 carbons, an ester group comprising 1 to 20 carbons,an amide group comprising 1 to 20 carbons, an aryl group comprising 1 to20 carbons, or an alkoxy group comprising 1 to 20 carbons; and each R″independently represents an alkyl group comprising 1 to 20 carbons or anaryl group comprising 1 to 20 carbons. The R′ and R″ groups canindependently comprise a cycloaliphatic ring, an aromatic ring, or aheteroatom such as oxygen, sulfur or nitrogen. When n is 0, the carbonsattached to each X group are linked together by a single bond.

Thus, the precursor compound comprises at least the two carbons and twoX groups. More particularly, the precursor compound has a functionalgroup selected from 1,2-ethanediol group, 1,3-propanediol group,1,4-butanediol group, 1,2-ethanediamine group, 1,3-propanediamine group,1,4-butanediamine group, 2-aminoethanol group, 3-amino-1-propanol group,4-amino-1-butanol group, 2-mercaptoethanol group, 3-mercapto-1-propanolgroup, 1-mercapto-2-propanol group, 4-mercapto-1-butanol group,cysteamine group, 1,2-ethanedithiol group, 1,3-propanedithiol group, orcombinations thereof. In one embodiment, the PFC does not react with anyR′ group.

The precursor compounds can also include isomerically pure forms of thecompounds and racemic mixtures. The isomerically pure compounds can havean enantiomeric excess of at least 90%, more specifically at least 95%,and even more specifically at least 98%.

Scheme 1 illustrates reactions using PFC and a catalyst to producevarious cyclic monomers: trimethylene carbonate (3) from 1,3-propanediol(2); trimethylene urea (5) from 1,3-propanediamine (4), trimethylenecarbamate (7) from 3-amino-1-propanol (6), trimethylene thiocarbonate(9) from 3-mercapto-1-propanol (8); and trimethylene dithiocarbonate(11) from 1,3-propanedithiol.

While a cyclic monomer such as (3) can be organocatalyticallypolymerized to form biocompatible and degradable materials, priorsyntheses of (3) have required the use of toxic reagents such asphosgene or triphosgene. The procedures also involved workups requiringsubstantial time and energy that diminished the overall “greenness” ofthe process. PFC overcomes these issues and vastly improves the cost,safety, and environmental impact of producing cyclic monomers.

Cyclic monomers produced by the disclosed method are represented by thegeneral formula (12):

where each Y independently represents O, S, NH or NR″; each R′independently represents a hydrogen, a halide, an alkyl group comprising1 to 20 carbons, an ester group comprising 1 to 20 carbons, an amidegroups comprising 1 to 20 carbons, an aryl group comprising 1 to 20carbons, or an alkoxy group comprising 1 to 20 carbons; each R″independently represents an alkyl group comprising 1 to 20 carbons or anaryl group comprising 1 to 20 carbons; and n is 0 to 6. When n is 0, themethylene carbons bonded to each Y group are linked together by a singlebond.

Exemplary substituted precursor compounds, where at least one R′ groupin formula (I) is a substituent other than hydrogen, include thematerials of general formula (13):

where X and R′ have the meaning described above for formula (I); X′represents O, S, NH, or NR″ where R″ has the meaning described above forformula (I); R′″ represents an alkyl group comprising 1 to 20 carbons,or an aryl group comprising 1 to 20 carbons; and z is 0 or 1. In oneembodiment, each X in formula (13) is OH, X′ is O, R′ is a methyl orethyl group, z is 1, and R′″ is selected from the group consisting ofmethyl, ethyl, propyl, isopropyl, n-butyl, t-butyl, sec-butyl, n-pentyl,neo-pentyl, iso-pentyl, phenyl, pentafluorophenyl, xylyl,para-methoxyphenyl, benzyl, pentafluorobenzyl, n-octyl, and naphthyl.

The corresponding cyclic monomer formed by the precursor compounds offormula (13) have the general structure (14):

where Y, R′, X′, R′″ and z have the same meaning described above.

Another challenge in preparing cyclic monomers, such as cycliccarbonates from 1,3-diols, is achieving selective ring closure withoutpolymerization, which depends on the nucleophilicity of the leavinggroup and the catalyst used. During reaction of the precursor compound,PFC and catalyst, a pentafluorophenol byproduct is formed. Thepentafluorophenol byproduct is a weak nucleophile and does not initiatepolymerization. By comparison, when PFC is substituted with dimethylcarbonate, methanol is produced as the leaving group. Methanol is astronger nucleophile than pentafluorophenol and causes significantamounts of undesirable polymer to be formed rather than the cycliccarbonate. In another example, when PFC is substituted with diimidazolecarbonate, imidazole is released. Imidazole facilitates ring-closure andconcurrent polymerization by activating the alcohol as an initiator.Thus, PFC is preferred over dimethyl carbonate or diimidazole carbonatesince it produces less undesirable polymer byproduct. In an embodiment,the disclosed method produces 0 to less than 0.5 wt % polymer byproductderived from the precursor compound, based on the weight of precursorcompound. In another embodiment, the disclosed method produces nodetectable polymer byproduct derived from the precursor compound.

The first mixture also includes a catalyst suitably chosen to activatethe nucleophilic diol, amino-alcohol, diamine, mercapto-alcohol,amino-thiol, or dithiol functional groups and not the electrophilic PFCcarbonyl group. Exemplary catalysts include tertiary amines, for example1,8-bis(dimethylamino)naphthalene, referred to also as PROTON SPONGE, atrademark of Sigma-Aldrich. Other catalysts include halide salts ofGroup I elements, particularly lithium (Li), sodium (Na), potassium (K),rubidium (Rb), cesium (Cs), or francium (Fr). In one embodiment thecatalyst is CsF.

The catalyst can be present in an amount of 0.02 to 1.00 moles per moleof the precursor compound, more particularly 0.05 to 0.50 moles per moleof the precursor compound, and even more particularly 0.15 to 0.25 molesper mole of the precursor compound.

The first mixture can optionally include a solvent such astetrahydrofuran, methylene chloride, chloroform, acetone, methyl ethylketone, acetonitrile, ethyl acetate, butyl acetate, benzene, toluene,xylene, hexane, petroleum ethers, 1,4-dioxane, diethyl ether, ethyleneglycol dimethyl ether, or combinations thereof. When a solvent ispresent, the concentration of precursor compound in the solvent can be0.02 to 0.8 moles per liter, more specifically 0.1 to 0.6 moles perliter, or most specifically 0.15 to 0.25 moles per liter. In oneembodiment, the reaction mixture consists of the precursor compound,PFC, a catalyst and a solvent. In one embodiment the solvent isanhydrous.

The method includes agitating the first mixture at a temperaturesuitable for converting the precursor compound to the cyclic monomer.The temperature can be from −20° C. to 100° C., 0° C. to 80° C., 10° C.to 50° C., or more specifically ambient or room temperature, typically17° C. to 30° C. Optionally, the reaction mixture is agitated under aninert atmosphere. In one embodiment, the temperature is ambienttemperature. The first mixture can be heated by conventional techniquesinvolving resistive elements, or by microwaves. Microwaves cansubstantially reduce reaction times.

Agitation of the first mixture can be conducted for 1 hour to 120 hours,5 hours to 48 hours, and more specifically 12 hours to 36 hours. In oneembodiment, agitation is conducted for 15 to 24 hours at ambienttemperature.

Agitation results in a second mixture comprising the cyclic monomer andthe pentafluorophenol byproduct. The cyclic monomer can be isolatedusing any known method of purification, including distillation,chromatography, extraction, and precipitation. In one embodiment, thecyclic monomer is purified by selective precipitation of thepentafluorophenol byproduct or the cyclic monomer from the secondmixture. In one variation on selective precipitation, the reactionmixture comprises a first solvent in which the precursor compound, PFC,cyclic monomer and pentafluorophenol byproduct are highly soluble. Uponcompletion of the reaction to form the cyclic monomer, the first solventis removed by, for example, vacuum distillation, followed by addition ofa second solvent suitably chosen to selectively precipitate thepentafluorophenol byproduct or the cyclic monomer. In another variation,the first solvent can be selected to facilitate precipitation of thecyclic monomer or the pentafluorophenol byproduct from the secondmixture as the reaction proceeds.

The method can further comprise the step of recovering thepentafluorophenol byproduct for recycling. Because the disclosedcyclization reactions do not consume pentafluorophenol, two moles ofpentafluorophenol are produced for every mole of PFC used. Generally,the yield of recovered pentafluorophenol byproduct from the secondmixture is about 100 to 200 mole percent, more particularly 150 to 200mole percent, and even more particularly 180 to 200 mole percent basedon moles of PFC used in the first mixture. In an embodiment, thepentafluorophenol is quantitatively recovered from the second mixture.

Also disclosed are the cyclic monomers produced by the above-describedmethod, wherein the cyclic monomer is derived frombis(pentafluorophenyl)carbonate and a precursor compound selected fromthe group consisting of diol, amino-alcohol, diamine, mercapto-alcohol,amino-thiol, and dithiol, and combinations thereof. More specifically,the cyclic monomer can be a cyclic carbonate selected from the groupconsisting of dimethylene carbonate, propylene carbonate, trimethylenecarbonate, tetramethylene carbonate, pentamethylene carbonate, andMTC-Bn. Further, the cyclic monomer can be a cyclic carbamate selectedfrom the group consisting of dimethylene carbamate, propylene carbamate,trimethylene carbamate (TMU), tetramethylene carbamate, andpentamethylene carbamate. Still further, the cyclic monomer can be acyclic urea selected from the group consisting of dimethylene urea,trimethylene urea, tetramethylene urea, and pentamethylene urea. Yetanother cyclic monomer can be a cyclic thiocarbonate selected from thegroup consisting of dimethylene thiocarbonate, propylene thiocarbonate,trimethylene thiocarbonate, tetramethylene thiocarbonate. Still anothercyclic monomer can be a cyclic thiocarbamate selected from the groupconsisting of dimethylene thiocarbamate, propylene thiocarbamate,trimethylene thiocarbamate, tetramethylene thiocarbmate. Finally, thecyclic monomer can be a cyclic dithiocarbonate selected from the groupconsisting of dimethylene thiocarbonate, propylene thiocarbonate,trimethylene thiocarbonate, tetramethylene thiocarbonate.

The cyclic monomers include isomerically pure forms of the cyclicmonomers and racemic mixtures.

The cyclic monomers can undergo ring-opening polymerization (ROP) toform biodegradable polymers of different tacticities. Atactic,syndiotactic and isotactic forms of the polymers can be produced thatdepend on the cyclic monomer(s), its isomeric purity, and thepolymerization conditions.

A method of ring-opening polymerization comprises forming a firstmixture comprising the cyclic monomer, a catalyst, an initiator, and anoptional solvent. The first mixture is then heated and agitated toeffect polymerization of the cyclic monomer, forming a second mixturecontaining the biodegradable polymer product.

The ring opening polymerization is generally conducted in a reactorunder inert atmosphere such as nitrogen or argon. The polymerization canbe performed by solution polymerization in an inactive solvent such asbenzene, toluene, xylene, cyclohexane, n-hexane, dioxane, chloroform anddichloroethane, or by bulk polymerization. The ROP reaction temperaturecan be from about room temperature to 250° C. Generally, the reactionmixture is heated at atmospheric pressure for 0.5 to 72 hours to effectpolymerization. Subsequently, additional cyclic monomer and catalyst canbe added to the second mixture to effect block polymerization ifdesired.

Exemplary catalysts for the ROP polymerization include metal oxides suchas tetramethoxy zirconium, tetra-iso-propoxy zirconium, tetra-iso-butoxyzirconium, tetra-n-butoxy zirconium, tetra-t-butoxy zirconium, triethoxyaluminum, tri-n-propoxy aluminum, tri-iso-propoxy aluminum, tri-n-butoxyaluminum, tri-iso-butoxy aluminum, tri-sec-butoxy aluminum,mono-sec-butoxy-di-iso-propoxy aluminum, ethyl acetoacetate aluminumdiisopropylate, aluminum tris(ethyl acetoacetate), tetraethoxy titanium,tetra-iso-propoxy titanium, tetra-n-propoxy titanium, tetra-n-butoxytitanium, tetra-sec-butoxy titanium, tetra-t-butoxy titanium,tri-iso-propoxy gallium, tri-iso-propoxy antimony, tri-iso-butoxyantimony, trimethoxy boron, triethoxy boron, tri-iso-propoxy boron,tri-n-propoxy boron, tri-iso-butoxy boron, tri-n-butoxy boron,tri-sec-butoxy boron, tri-t-butoxy boron, tri-iso-propoxy gallium,tetramethoxy germanium, tetraethoxy germanium, tetra-iso-propoxygermanium, tetra-n-propoxy germanium, tetra-iso-butoxy germanium,tetra-n-butoxy germanium, tetra-sec-butoxy germanium and tetra-t-butoxygermanium; halogenated compound such as antimony pentachloride, zincchloride, lithium bromide, tin(IV) chloride, cadmium chloride and borontrifluoride diethyl ether; alkyl aluminum such as trimethyl aluminum,triethyl aluminum, diethyl aluminum chloride, ethyl aluminum dichlorideand tri-iso-butyl aluminum; alkyl zinc such as dimethyl zinc, diethylzinc and diisopropyl zinc; tertiary amines such as triallylamine,triethylamine, tri-n-octylamine and benzyldimethylamine; heteropolyacidssuch as phosphotungstic acid, phosphomolybdic acid, silicotungstic acidand alkali metal salt thereof; zirconium compounds such as zirconiumacid chloride, zirconium octanoate, zirconium stearate and zirconiumnitrate. More particularly, the catalyst is zirconium octanoate,tetraalkoxy zirconium or a trialkoxy aluminum compound.

Other ROP catalysts include metal-free organocatalysts that can providea platform to polymers having controlled, predictable molecular weightsand narrow polydispersities. Examples of organocatalysts for the ROP ofcyclic esters, carbonates and siloxanes are 4-dimethylaminopyridine,phosphines, N-heterocyclic carbenes (NHC), bifunctional aminothioureas,phosphazenes, amidines, and guanidines.

The ROP reaction mixture comprises at least one catalyst and, whenappropriate, several catalysts together. The ROP catalyst is added in aproportion of 1/20 to 1/40,000 moles relative to the cyclic monomers,and preferably of 1/1,000 to 1/20,000 moles.

The ROP reaction mixture also comprises an initiator. Initiatorsgenerally include nucleophiles such as alcohols, amines and thiols. Theinitiator can be monofunctional, difunctional or multifunctional such asdendritic, polymeric or related architectures. Monofunctional initiatorscan include nucleophiles with protected functional groups that includethiols, amines, acids and alcohols. A typical initiator is phenol orbenzyl alcohol.

Well-known apparatuses can be used for performing the ROPpolymerization. An example of a tower type reaction apparatus ise areaction vessel comprising helical ribbon wings and transformationalspiral baffles. An example of sideways type reaction apparatus is asideways type one- or twin-shaft kneader comprising agitation shaftswhich have a row of transformational wings and arranged in parallel toeach other. In addition, the reaction apparatus may be either a batchtype or a continuous one.

The biodegradable ROP product can be in the form of a homopolymer,copolymer, or block copolymer. The biodegradable polymer can have anumber-average molecular weight of usually 1,000 to 200,000, moreparticularly 2,000 to 100,000, and still more particularly 5,000 to80,000.

The biodegradable polymer product of the ROP polymerization can beapplied to conventional molding methods such as extrusion molding,injection molding, hollow molding and vacuum molding, and can beconverted to molded articles such as various parts, receptacles,materials, tools, films, sheets and fibers. A molding composition can beprepared comprising the biodegradable polymer and various additives,including for example nucleating agents, pigments, dyes, heat-resistingagents, antioxidants, weather-resisting agents, lubricants, antistaticagents, stabilizers, fillers, strengthened materials, fire retardants,plasticizers, and other polymers. Generally, the molding compositionscomprise 30 wt. % to 100 wt. % or more of the biodegradable polymerbased on total weight of the molding composition. More particularly, themolding composition comprises 50 wt. % to 100 wt. % of the biodegradablepolymer.

The following examples illustrate the method of preparing a cyclicmonomer.

EXAMPLES Examples 1-3 Preparation ofMethyl-5-Benzyloxycarboxyl-1,3-Dioxan-2-One (MTC-Bn)—Optimization ofSolvent

Example 1

In a flask, benzyl 2,2-bis(methylol)propionate (Bn-MPA) (0.500 g,0.00222 mol, 1 eq.) was placed in tetrahydrofuran (THF, 20 ml), followedby PFC (0.875 g, 0.00222 mol, 1 eq.). CsF (84 mg, 0.555 mmol, 0.25 eq.)was added as a solid, and the solution was stirred for 24 hours at roomtemperature. A small aliquot was dried, and the solvent was replacedwith CDCl₃. Proton NMR of the crude product indicated approximately 70%conversion to 5-methyl-5-benzyloxycarboxyl-1,3-dioxan-2-one (MTC-Bn),and no trace of polycarbonate.

Example 2

In a flask, Bn-MPA (0.500 g, 0.00222 mol, 1 eq.) was placed indichloromethane (DCM, 15 ml), followed by PFC (0.875 g, 0.00222 mol, 1eq.). CsF (84 mg CsF, 0.555 mmol, 0.25 eq.) was added as a solid, andthe solution was stirred for 24 hours at room temperature. A smallaliquot was dried out, and the solvent was replaced by CDCl₃. Proton NMRof the crude indicated approximately 50% conversion to MTC-Bn, and notrace of polycarbonate.

Example 3

In a flask, Bn-MPA (0.500 g, 0.00222 mol, 1 eq.) was placed in acetone(20 ml), followed by PFC (0.875 g, 0.00222 mol, 1 eq.). CsF (84 mg,0.555 mmol, 0.25 eq.) was added as a solid, and the solution was stirredfor 24 hours at room temperature. A small aliquot was dried, and thesolvent was replaced by CDCl₃. Proton NMR of the crude indicatedapproximately 90% conversion to MTC-Bn, and no trace of polycarbonate.

Examples 4-5 Preparation of MTC-Bn—Optimization of Stoichiometry Example4

In a flask, Bn-MPA (0.250 g, 0.00111 mol, 1 eq.) was placed in THF (15ml), followed by PFC (0.660 g, 0.00333 mol, 1.5 eq.). CsF (42 mg, 0.277mmol, 0.25 eq.) was added as a solid, and the solution was stirred for24 hours at room temperature. A small aliquot was dried, and the solventwas replaced by CDCl₃. Proton NMR of the crude indicated approximately95% conversion to MTC-Bn, and no trace of polycarbonate.

Example 5

In a flask, Bn-MPA (0.250 g, 0.00111 mol, 1 eq.) was placed in THF (15ml), followed by PFC (0.660 g, 0.00166 mol, 1.5 eq.). CsF (42 mg, 0.277mmol, 0.25 eq.) was added as a solid, and the solution was stirred for24 hours at room temperature. A small aliquot was dried out, and solventwas replaced by CDCl₃. Proton NMR of the crude indicates approximately95% conversion to MTC-Bn, and more importantly no trace ofpolycarbonate.

Examples 6 Preparation of MTC-Bn with PROTON SPONGE Example 6

In a flask, Bn-MPA (0.500 g, 0.00222 mol, 1 eq.) was placed in THF,followed by PFC (0.875 g, 0.00222 mol, 1 eq.). Then PROTON SPONGE (119mg, 0.555 mmol, 0.25 eq.) was added, and solution was stirred for 24hours at room temperature. A small aliquot was dried, and the solventwas replaced by CDCl₃. Proton NMR of the crude indicates approximately70% conversion to MTC-Bn, and no trace of polycarbonate. The solutioncolor was pink/orange.

Example 7 Preparation of MTC-Bn with CsF Example 7

In a 20 mL glass vial, Bn-MPA (500 mg, 2.25 mmol),bis(pentafluorophenyl)carbonate (1.32 g, 3.35 mmol), cesium fluoride (67mg, 0.44 mmol, 0.20 eq), and dry THF (5 mL) were added and stirred for16 hours at room temperature. After the solvent was evaporated from theinhomogeneous mixture methylene chloride (15 mL) was added to theresidue, and the insoluble material was filtered. The filtrate was thenwashed with saturated aqueous NaHCO₃ (2×20 mL), dried over MgSO₄,filtered and evaporated to give MTC-Bn as a white solid (402 mg, 71.6%).

Example 8 Synthesis of trimethyleneurethane (TMU)

Example 8

3-Amino-1-propanol, (6), (2.29 mL, 30.0 mmol) was dissolved in THF (40mL) in a 100 mL round-bottom flask and the solution was cooled to −5° C.with ice-salt bath. A solution of PFC (13.02 g, 33.1 mmol) in dry THF(25 mL) was added stepwise over 30 min, at which point the reactionmixture was allowed to warm to room temperature for 2 hours. CsF (0.91g, 6.0 mmol, 0.20 eq) was added to the mixture prior to overnightstirring. The solvent was removed in vacuo, and the resulting residuewas dissolved in methylene chloride, cooled and filtered to removeinsoluble material. The filtrate was dried under vacuum to yield a paleamber solid as a crude product, which was recrystallized in a mixture ofethyl acetate and hexane. The crystalline compound was then heated toabout 100° C. under vacuum until no signal was observed in ¹⁹F NMR. Themolten residue was cooled to room temperature to provide the isolatedproduct, TMU, as a white solid (1.86 g, 61.2%). ¹H NMR (400 MHz, CDCl₃):δ 5.87 (b, 1H, NH), 4.30 (t, 2H, CH₂O), 3.38-3.36 (m, 2H, CH₂N),2.02-1.96 (m, 2H, CH₂). ¹³C NMR (100 MHz, DMSO-d₆): δ 152.7, 66.1, 38.8,20.9.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Asused herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” when used in this specification, specify thepresence of stated features, integers, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, integers, steps, operations, element components,and/or groups thereof.

The corresponding structures, materials, acts, and equivalents of allmeans or step plus function elements in the claims below are intended toinclude any structure, material, or act for performing the function incombination with other claimed elements as specifically claimed. Thedescription of the present invention has been presented for purposes ofillustration and description, but is not intended to be exhaustive orlimited to the invention in the form disclosed. Many modifications andvariations will be apparent to those of ordinary skill in the artwithout departing from the scope and spirit of the invention.

While preferred embodiments to the invention have been described, itwill be understood that those skilled in the art, both now and in thefuture, may make various changes that fall within the scope of theclaims which follow. These claims should be construed to maintain theproper protection for the invention described.

1. A method of preparing a cyclic monomer, comprising: forming a firstmixture comprising a precursor compound, bis(pentafluorophenyl)carbonate, and a catalyst; wherein the precursor compound has astructure comprising a) two or more carbons, and b) two functionalgroups independently selected from the group consisting of primaryamine, secondary amine, thiol group, hydroxyl group, and combinationsthereof; and agitating the first mixture at a temperature effective toform a second mixture comprising the cyclic monomer, the cyclic monomerselected from the group consisting of a cyclic carbonate, a cycliccarbamate, a cyclic urea, a cyclic thiocarbonate, a cyclicthiocarbamate, and a cyclic dithiocarbonate.
 2. The method of claim 1wherein the first mixture comprises a solvent.
 3. The method of claim 1,wherein the catalyst is a tertiary amine.
 4. The method of claim 1,wherein the catalyst is 1,8-bis(dimethylamino)naphthalene.
 5. The methodof claim 1, wherein the catalyst is a halide salt of at least one of thefollowing: lithium, sodium, potassium, rubidium, and cesium.
 6. Themethod of claim 1, wherein the reaction mixture comprises from 0 to lessthan 0.5 wt % of a polymer byproduct derived from the precursorcompound, based on a weight of precursor compound.
 7. The method ofclaim 1, wherein the precursor compound has an asymmetric center, andthe precursor compound has an isomeric purity characterized by anenantiomeric excess of 80% to 100%.
 8. The method of claim 1, whereinagitating the reaction mixture at ambient temperature forms apentafluorophenol byproduct, and the method further comprises recoveringthe pentafluorophenol byproduct.
 9. The method of claim 1, wherein thecyclic carbonate is selected from the group consisting of dimethylenecarbonate, propylene carbonate, trimethylene carbonate, tetramethylenecarbonate, and pentamethylene carbonate.
 10. The method of claim 1,wherein the cyclic carbamate is selected from the group consisting ofdimethylene carbamate, propylene carbamate, trimethylene carbamate(TMU), tetramethylene carbamate, and pentamethylene carbamate.
 11. Themethod of claim 1, wherein the cyclic urea monomer is selected from thegroup consisting of dimethylene urea, trimethylene urea, tetramethyleneurea, and pentamethylene urea.
 12. The method of claim 1, wherein thecyclic thiocarbonate monomer is selected from the group consisting ofdimethylene thiocarbonate, propylene thiocarbonate, trimethylenethiocarbonate, and tetramethylene thiocarbonate.
 13. The method of claim1, wherein the cyclic thiocarbamate monomer is selected from the groupconsisting of dimethylene thiocarbamate, propylene thiocarbamate,trimethylene thiocarbamate, and tetramethylene thiocarbamate.
 14. Themethod of claim 1, wherein the cyclic dithiocarbonate monomer isselected from the group consisting of dimethylene dithiocarbonate,propylene dithiocarbonate, trimethylene dithiocarbonate, tetramethylenedithiocarbonate.
 15. A method of preparing a cyclic monomer, comprising:forming a first mixture comprising a bis(pentafluorophenyl)carbonate, acatalyst, and a precursor compound of the general formula (1):

wherein each X group independently represents OH, NHR″, NH₂, or SH; n is0 to 6; each R′ independently represents a hydrogen, a halide, an alkylgroup comprising 1 to 20 carbons, an ester group comprising 1 to 20carbons, an amide group comprising 1 to 20 carbons, an aryl groupcomprising 1 to 20 carbons, or an alkoxy group comprising 1 to 20carbons; and each R″ independently represents an alkyl group comprising1 to 20 carbons or an aryl group comprising 1 to 20 carbons; andagitating the first mixture at a temperature effective to form a secondmixture comprising the cyclic monomer, the cyclic monomer selected fromthe group consisting of a cyclic carbonate, a cyclic carbamate, a cyclicurea, a cyclic thiocarbonate, a cyclic thiocarbamate, and a cyclicdithiocarbonate.
 16. The method of claim 15, wherein thebis(pentafluorophenyl)carbonate reacts only with the two X groups. 17.The method of claim 15, wherein each X group is OH.
 18. The method ofclaim 15, wherein one X group is OH, and another X group is NH₂.
 19. Themethod of claim 15, wherein n is
 1. 20. The method of claim 15, whereinthe cyclic monomer is a cyclic carbonate.
 21. The method of claim 15,wherein the cyclic monomer is a cyclic carbamate.
 22. The method ofclaim 15, wherein the catalyst is cesium fluoride.
 23. The method ofclaim 15, wherein the cyclic monomer has the general structure (12):

wherein each Y independently represents O, S, NH or NR″; each R′independently represents a hydrogen, a halide, an alkyl group comprising1 to 20 carbons, an ester group comprising 1 to 20 carbons, an amidegroups comprising 1 to 20 carbons, an aryl group comprising 1 to 20carbons, or an alkoxy group comprising 1 to 20 carbons; each R″independently represents an alkyl group comprising 1 to 20 carbons or anaryl group comprising 1 to 20 carbons; and n is 0 to
 6. 24. The methodof claim 23, wherein each Y is O.
 25. The method of claim 23, whereinone Y is O, and another Y is NH.
 26. The method of claim 23, wherein nis
 1. 27. A method of preparing a cyclic monomer, comprising: forming afirst mixture comprising bis(pentafluorophenyl)carbonate, a catalyst,and a precursor compound of the general formula (13):

wherein X independently represents OH, NHR″, NH₂, or SH; R′ represents ahydrogen, a halide, an alkyl group comprising 1 to 20 carbons, an estergroup comprising 1 to 20 carbons, an amide group comprising 1 to 20carbons, an aryl group comprising 1 to 20 carbons, or an alkoxy groupcomprising 1 to 20 carbons; X′ represents O, S, NH, or NR″; R″ in X andX′ independently represents an alkyl group comprising 1 to 20 carbons oran aryl group comprising 1 to 20 carbons; R′″ represents an alkyl groupcomprising 1 to 20 carbons, or an aryl group comprising 1 to 20 carbons;and z is 0 or 1; and agitating the first mixture at a temperatureeffective to form a second mixture comprising the cyclic monomer, thecyclic monomer selected from the group consisting of a cyclic carbonate,a cyclic carbamate, a cyclic urea, a cyclic thiocarbonate, a cyclicthiocarbamate, and a cyclic dithiocarbonate.
 28. The method of claim 27,wherein each X is OH.
 29. The method of claim 27, wherein one X is OH,and another X is NH₂.
 30. The method of claim 27, wherein the cyclicmonomer is a cyclic carbonate.
 31. The method of claim 27, wherein thecyclic monomer is a cyclic carbamate.
 32. The method of claim 27,wherein the bis(pentafluorophenyl)carbonate reacts only with the Xgroups.
 33. The method of claim 27, wherein the cyclic monomer has thegeneral structure (14):

wherein Y independently represents O, S, NH or NR″; X′ represents O, S,NH, or NR″; each R′ independently represents a hydrogen, a halide, analkyl group comprising 1 to 20 carbons, an ester group comprising 1 to20 carbons, an amide groups comprising 1 to 20 carbons, an aryl groupcomprising 1 to 20 carbons, or an alkoxy group comprising 1 to 20carbons; each R″ in Y and X′ independently represents an alkyl groupcomprising 1 to 20 carbons or an aryl group comprising 1 to 20 carbons;R′ represents an alkyl group comprising 1 to 20 carbons, or an arylgroup comprising 1 to 20 carbons; and z is 0 or
 1. 34. The method ofclaim 33, wherein each Y is O.
 35. The method of claim 33, wherein one Yis O, and another Y is NH.
 36. The method of claim 33, wherein R′ ismethyl or ethyl.
 37. The method of claim 33, wherein X′ is 0 and z is 1.